MEK162 (ARRY-162, ARRY-438162)
ARRY-438162 is a potent inhibitor of MEK1/2 with IC50 of 12 nM.
CEP-32496 is a highly potent inhibitor of BRAF(V600E/WT) and c-Raf with Kd of 14 nM/36 nM and 39 nM, also potent to Abl-1, c-Kit, Ret, PDGFRβ and VEGFR2, respectively; insignificant affinity for MEK-1, MEK-2, ERK-1 and ERK-2. Phase 1/2.
Features:High binding affinity for both BRAF (V600E) mutation and related c-Raf, but no significant affinity for other kinases of MAPK pathway.
Sorafenib is a multikinase inhibitor of Raf-1, B-Raf and VEGFR-2 with IC50 of 6 nM, 22 nM and 90 nM, respectively.
Selumetinib (AZD6244) is a potent, highly selective MEK1 inhibitor with IC50 of 14 nM, also inhibits ERK1/2 phosphorylation with IC50 of 10 nM, no inhibition to p38α, MKK6, EGFR, ErbB2, ERK2, B-Raf, etc. Phase 1/2.
Features:First MEK inhibitor being tested in Phase II clinical trials.
PD0325901 (PD325901) is selective and non ATP-competitive MEK inhibitor with IC50 of 0.33 nM, roughly 500-fold more potent than CI-1040 on phosphorylation of ERK1 and ERK2. Phase 1/2.
Trametinib (GSK1120212) is a highly specific and potent MEK1/2 inhibitor with IC50 of 0.92 nM/1.8 nM, no inhibition of the kinase activities of c-Raf, B-Raf, ERK1/2. Phase 3.
Features:More potent than PD0325901 or AZD6244.
U0126-EtOH is a highly selective inhibitor of MEK1/2 with IC50 of 0.07 μM/0.06 μM, 100-fold higher affinity for ΔN3-S218E/S222D MEK than PD098059.
Features:A chemically synthesized and highly selective inhibitor of both MEK1 and MEK2.
CI-1040 (PD 184352) is an ATP non-competitive MEK1/2 inhibitor with IC50 of 17 nM, 100-fold more selective for MEK1/2 than MEK5. Phase 2.
Features:First MEK inhibitor to begin clinical development.
PD98059 is a non-ATP competitive MEK inhibitor with IC50 of 2 μM, specifically inhibits MEK-1-mediated activation of MAPK; does not directly inhibit ERK1 or ERK2.
Features:Does not inhibit c-Raf phosphorylated MEK1.
BIX02189 is a selective inhibitor of MEK5 with IC50 of 1.5 nM, also inhibits ERK5 catalytic activity with IC50 of 810 nM, and does not inhibit closely related kinases MEK1, MEK2, ERK2, and JNK2.